title: Bub1, Sgo1, and Mps1 mediate a distinct pathway for chromosome biorientation in budding yeast.
abstract: The conserved mitotic kinase Bub1 performs multiple functions that are only partially characterized. Besides its role in the spindle assembly checkpoint and chromosome alignment, Bub1 is crucial for the kinetochore recruitment of multiple proteins, among them Sgo1. Both Bub1 and Sgo1 are dispensable for growth of haploid and diploid budding yeast, but they become essential in cells with higher ploidy. We find that overexpression of SGO1 partially corrects the chromosome segregation defect of bub1Δ haploid cells and restores viability to bub1Δ tetraploid cells. Using an unbiased high-copy suppressor screen, we identified two members of the chromosomal passenger complex (CPC), BIR1 (survivin) and SLI15 (INCENP, inner centromere protein), as suppressors of the growth defect of both bub1Δ and sgo1Δ tetraploids, suggesting that these mutants die due to defects in chromosome biorientation. Overexpression of BIR1 or SLI15 also complements the benomyl sensitivity of haploid bub1Δ and sgo1Δ cells. Mutants lacking SGO1 fail to biorient sister chromatids attached to the same spindle pole (syntelic attachment) after nocodazole treatment. Moreover, the sgo1Δ cells accumulate syntelic attachments in unperturbed mitoses, a defect that is partially corrected by BIR1 or SLI15 overexpression. We show that in budding yeast neither Bub1 nor Sgo1 is required for CPC localization or affects Aurora B activity. Instead we identify Sgo1 as a possible partner of Mps1, a mitotic kinase suggested to have an Aurora B-independent function in establishment of biorientation. We found that Sgo1 overexpression rescues defects caused by metaphase inactivation of Mps1 and that Mps1 is required for Sgo1 localization to the kinetochore. We propose that Bub1, Sgo1, and Mps1 facilitate chromosome biorientation independently of the Aurora B-mediated pathway at the budding yeast kinetochore and that both pathways are required for the efficient turnover of syntelic attachments.
authors.affiliation: Department of Pediatric Oncology, Children's Hospital, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Storchová
authors.forename: Justin S
authors.initials: JS
authors.lastname: Becker
authors.forename: Nicolas
authors.initials: N
authors.lastname: Talarek
authors.forename: Sandra
authors.initials: S
authors.lastname: Kögelsberger
authors.forename: David
authors.initials: D
authors.lastname: Pellman
mesh_terms: D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D045584:Chromosome Positioning; D020090:Chromosome Segregation / Q000502:physiology; D015825:Chromosomes, Fungal; D018386:Kinetochores / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism
chemical_list: C546593:Bir1 protein, S cerevisiae; D002352:Carrier Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; C482640:Sgo1 protein, S cerevisiae; C480084:Sli15 protein, S cerevisiae; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases; C093416:MPS1 protein, S cerevisiae